Hepatocellular injury is common in HIV infection and can have multiple causes including alcohol use, antiretroviral therapy, hepatitis B, and hepatitis C. Hepatocellular injury as demonstrated by elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and v-glutamyl transferase (GGT) at baseline is associated with an increased risk of all-cause and liver-related mortality. Attempts to better understand the dynamics of hepatocellular injury and the relationship with alcohol use will lead to better care of HIV infected veterans and will provide a template for the study of alcohol use in the setting of other comorbid conditions. The objectives of this study are: (1) to characterize the effect of alcohol use patterns on the change in ALT, AST and GGT; (2) to characterize the impact of alcohol use on mortality; and (3) to estimate life expectancy stratified by alcohol use patterns and changes in ALT, AST and GGT for future cost-effectiveness studies. This project is a two-year project that begins with secondary data analysis of data collected through the Veterans Aging Cohort Study (VACS), an observational study enrolling HIV-infected and HIV-negative controls from 8 VA sites, and the Virtual VACS, an administrative cohort that includes pharmacy and laboratory data. The impact of alcohol use on changes in ALT, AST and GGT will be analyzed using several techniques including ANCOVA with the baseline value as a covariate, raw change score, and area under the curve. The impact of alcohol on mortality will be examined using life table and Kaplan Meier methodology. Cox models incorporating ALT, AST as time-varying covariates will examine the independent effect of alcohol use while adjusting for demographic factors, chronic viral hepatitis, antiretroviral use, and other substance use. Using insights gained from these analyses, a Markov simulation model will be developed to examine the estimated life expectancy in the setting of various patterns of alcohol use, incorporating the risk of hepatocellular injury and its relationship to future mortality. Because liver injury is quickly becoming a major cause of sickness and death for HIV-infected patients, understanding the impact of alcohol use in the presence of other potential causes of liver injury is needed to allow doctors to determine the best treatment for individual patients.